The whole topic in four terms
The circulation as a pressure–flow system
What you should already have
About 70 minutes
Plus the time it takes to redraw this lesson’s figures from memory, which is the fastest way to find out what you have not understood.
Where this shows up
This is the lesson the rest of cardiovascular physiology is derived from. The Wiggers diagram and the pressure–volume loop are the two drawings every later question returns to, and both are read rather than recalled: once the axes are right, the valve events, the phases and the effect of a changed preload all follow from the geometry.
Learning outcomes
By the end of this lesson you should be able to:
- Describe the circulation as a pressure–flow system, and state the equation that governs it with every symbol defined.
- Describe cardiac muscle and the conducting tissue, and explain excitation–contraction coupling from depolarisation to crossbridge cycling.
- Draw and label the Wiggers diagram with a time axis, the four valve events, and the atrial pressure waveform beneath it.
- Identify the a, c and v waves and the x and y descents, and say what each represents.
- Draw the pressure–volume loop with both axes scaled, label its four corners by valve event, and mark the ESPVR and EDPVR.
- Predict how the loop changes with a change in preload, afterload or contractility, and distinguish the three on the drawing.
Together these settle 2 syllabus objectives: Cardiac muscle, conducting tissue and excitation-contraction coupling and Cardiac cycle, pressure-flow relationships, heart sounds and valve activity. Tick them on the Physiology objective list once you can do all of the above without notes.
The circulation exists to deliver oxygen and substrate to tissue and to remove carbon dioxide and waste. It does this with two pumps in series driving two circuits in series, each of which distributes its flow to a set of organs in parallel. The parallel arrangement matters: it lets each organ set its own flow independently, and it means total peripheral resistance is lower than the resistance of any single bed.
The right ventricle is a volume pump — thin-walled, crescentic, working against a resistance about a tenth of the systemic one. The left ventricle is a pressure pump — thick-walled and near-cylindrical. They eject the same stroke volume, but the left does about five times the work, which is why left ventricular oxygen demand dominates the topic.
The governing equations
- CO — cardiac output, L min⁻¹
- HR — heart rate, beats min⁻¹
- SV — stroke volume, mL (as end-diastolic minus end-systolic volume)
- MAP — mean arterial pressure, mmHg
- SVR — systemic vascular resistance, mmHg min L⁻¹ (or dyn s cm⁻⁵ after multiplying by 80)
- RAP — right atrial pressure, mmHg; the downstream pressure, and usually small enough to omit
The weighting is not arbitrary: at a normal heart rate diastole occupies about two-thirds of the cycle, so the diastolic pressure is weighted twice. The approximation therefore fails at high heart rates, where diastole is proportionally shorter and mean pressure lies closer to the arithmetic mean.
- R — resistance to laminar flow
- η — viscosity of the fluid (eta), Pa s
- l — length of the tube, m
- r — radius of the tube, m
The fourth power is the whole point. Halving a vessel’s radius multiplies its resistance sixteenfold, which is why arterioles — the “resistance vessels” — control the distribution of flow, and why length, being anatomically fixed, is never the answer to a question about resistance.
- σ — wall stress (sigma), the force per unit area in the wall
- P — transmural pressure, mmHg
- r — internal radius, cm
- h — wall thickness, cm
This one equation explains why a dilated ventricle is mechanically disadvantaged, why hypertrophy is initially compensatory, why wall tension rather than pressure is the main determinant of myocardial oxygen demand, and why the thin-walled right ventricle copes with volume but not with pressure.
Normal values worth knowing exactly
| Variable | Typical value | Derivation | Range and note |
|---|---|---|---|
| Cardiac output | 5.0 L min⁻¹ | HR × SV | 4–8 L min⁻¹ at rest |
| Cardiac index | 3.0 L min⁻¹ m⁻² | CO ÷ body surface area | 2.5–4.0; removes body-size variation |
| Stroke volume | 70 mL | EDV − ESV | 60–100 mL |
| Stroke volume index | 40 mL m⁻² | SV ÷ BSA | 33–47 mL m⁻² |
| Ejection fraction | 58% | SV ÷ EDV | > 55% normal; load-dependent |
| End-diastolic volume | 120 mL | — | measured by echocardiography |
| End-systolic volume | 50 mL | — | rises with failure and with afterload |
| Heart rate | 70 min⁻¹ | — | intrinsic SA rate 90–120 without vagal tone |
| Mean arterial pressure | 93 mmHg | DBP + ⅓(SBP − DBP) | 70–105 mmHg |
| Central venous pressure | 3–5 mmHg | — | mean right atrial pressure |
| Pulmonary artery pressure | 24/8 mmHg | — | mean 9–16 mmHg |
| Pulmonary capillary wedge | 6–12 mmHg | — | surrogate for left atrial pressure |
| Systemic vascular resistance | 1100 dyn s cm⁻⁵ | 80 × (MAP − CVP) ÷ CO | 900–1400 |
| Pulmonary vascular resistance | 100 dyn s cm⁻⁵ | 80 × (mPAP − PCWP) ÷ CO | roughly a tenth of SVR |
| Mean systemic filling pressure | 7 mmHg | — | pressure with the circulation stopped |
| Total blood volume | 70 mL kg⁻¹ | ≈ 5 L in a 70 kg adult | 80–90 mL kg⁻¹ in the neonate |
Where the output goes
Distribution is set by the same equation as everything else: each organ receives a share determined by its own resistance relative to the rest, at a shared driving pressure. Note how poorly flow and oxygen consumption correlate — the kidney takes a fifth of the output and consumes 7% of the oxygen, while the heart takes 5% and consumes 11%.
| Organ | Blood flow (% of CO) | O₂ consumption (% of total) | Comment |
|---|---|---|---|
| Liver and splanchnic | 1500 mL (25–30%) | 50 mL min⁻¹ (20%) | Large flow, modest extraction; the first bed sacrificed in shock |
| Kidney | 1100 mL (20–25%) | 18 mL min⁻¹ (7%) | Flow greatly exceeds metabolic need — it is a filter, not a consumer |
| Skeletal muscle | 1000 mL (15–20%) | 50 mL min⁻¹ (20%) | Enormous reserve: can rise more than twentyfold in exercise |
| Brain | 750 mL (14%) | 45 mL min⁻¹ (18%) | Tightly autoregulated between about 50 and 150 mmHg |
| Skin | 500 mL (10%) | 12 mL min⁻¹ (5%) | Thermoregulatory, with arteriovenous anastomoses |
| Heart | 250 mL (4–5%) | 29 mL min⁻¹ (11%) | Highest extraction of any organ — about 70% at rest |
Cell to chamber
Cardiac muscle, conduction and excitation–contraction coupling
Structure that explains function
- Striated, branched and short. Each cell is about 100 µm long and 20 µm wide, with a single central nucleus and abundant mitochondria — roughly a third of cell volume, against about 2% in skeletal muscle, reflecting an almost entirely aerobic metabolism.
- Intercalated discs join cells end to end and carry three junction types: gap junctions (connexons) allowing ions and small molecules to pass, so the myocardium behaves as a functional syncytium; fascia adherens anchoring actin filaments so that force is transmitted from cell to cell; and desmosomes holding the cells together mechanically.
- T tubules are wide and aligned with the Z line, so depolarisation reaches the interior of every myofibril essentially at once. They form dyads with the sarcoplasmic reticulum rather than the triads of skeletal muscle.
- Two syncytia, not one. Atria and ventricles are electrically separated by the fibrous annulus, so the only normal route between them is the atrioventricular node and the bundle of His. That is what makes the AV nodal delay possible, and what makes complete heart block a discrete lesion.
Excitation–contraction coupling, step by step
| Step | What happens | Why it matters |
|---|---|---|
| 1 · Depolarisation | The action potential spreads along the sarcolemma and down the T tubules | T tubules are wide and align with the Z line, so every myofibril is reached almost simultaneously |
| 2 · Trigger calcium | Phase 2 opens L-type calcium channels (dihydropyridine receptors) in the T tubule membrane | The inward calcium current is small in amount but decisive in effect |
| 3 · Calcium-induced calcium release | Trigger calcium opens ryanodine receptors (RyR2) on the adjacent sarcoplasmic reticulum | This is the amplification step, and the one that distinguishes cardiac from skeletal muscle, where the coupling is mechanical rather than chemical |
| 4 · Activation | Cytosolic calcium rises from about 100 nmol L⁻¹ to 1–10 µmol L⁻¹ and binds troponin C | Tropomyosin moves off the myosin-binding site on actin |
| 5 · Cross-bridge cycling | Myosin heads bind actin, undergo the power stroke, and detach when new ATP binds | ATP is required for detachment as well as for contraction — which is why rigor follows ATP depletion |
| 6 · Relaxation | SERCA2a pumps calcium back into the sarcoplasmic reticulum; the Na⁺/Ca²⁺ exchanger and the sarcolemmal Ca²⁺-ATPase extrude the rest | Active and ATP-dependent, so relaxation fails before contraction in ischaemia |
Conduction
| Tissue | Conduction velocity (m s⁻¹) | Intrinsic rate (min⁻¹) | Note |
|---|---|---|---|
| SA node | 0.05 | 60–100 | Primary pacemaker; artery from the RCA in 60% and the circumflex in 40% |
| Atrial muscle | 1.0 | — | Spreads to the AV node partly by preferential internodal pathways |
| AV node | 0.05 | 40–60 | Deliberately slow: the delay allows atrial contraction to complete before ventricular systole, and protects the ventricle in atrial tachyarrhythmia |
| Bundle of His | 1.0 | 40–60 | The only normal electrical connection between atria and ventricles |
| Purkinje fibres | 2.0–4.0 | 20–40 | Fastest conduction in the heart; produces near-synchronous ventricular activation |
| Ventricular muscle | 0.3–1.0 | 20–40 | Endocardium to epicardium, apex to base |
Two features are worth stating explicitly. The atrioventricular nodal delay — about 0.1 s, seen on the surface ECG as most of the PR interval — is not an imperfection; it allows atrial contraction to complete before the ventricle begins, and its decremental conduction protects the ventricle from being driven at atrial rates in flutter or fibrillation. And the hierarchy of intrinsic rates means that every part of the conducting system is a potential pacemaker, with the fastest normally suppressing the rest by overdrive.
Contractility and how it is changed
Contractility is the intrinsic ability of the myocardium to generate force at a given preload and afterload. Everything that alters it does so by changing the amount of calcium delivered to troponin C per beat, or the sensitivity of troponin C to the calcium that arrives.
| Mechanism | Pathway | Effect | Examples |
|---|---|---|---|
| Sympathetic β₁ stimulation | Gs → adenylyl cyclase → cAMP → protein kinase A | Phosphorylates L-type channels (more Ca²⁺ entry), phospholamban (faster SERCA, so lusitropy) and troponin I | Adrenaline, dobutamine, sympathetic drive |
| Phosphodiesterase inhibition | Blocks cAMP breakdown | Same end point without the receptor; also vasodilates — an inodilator | Milrinone, enoximone |
| Calcium sensitisation | Increases troponin C affinity for calcium | Inotropy without increasing calcium load, so less arrhythmogenic and less oxygen-costly | Levosimendan |
| Na⁺/K⁺-ATPase inhibition | Raises intracellular Na⁺, so the Na⁺/Ca²⁺ exchanger extrudes less Ca²⁺ | Sarcoplasmic reticulum calcium content rises | Digoxin |
| Increased heart rate | Treppe or Bowditch effect | Less time per cycle for calcium extrusion, so sarcoplasmic reticulum stores accumulate | Physiological, and modest in humans |
| Increased afterload | Anrep effect | An acute rise in afterload produces a slow increase in contractility over minutes | Homeometric autoregulation |
Pressure, valves and volume
The cardiac cycle, the Wiggers diagram and the venous waveform
The seven phases
| Phase | Duration | Valves | Pressures (mmHg) | LV volume (mL) | ECG | Sound |
|---|---|---|---|---|---|---|
| Atrial systole | 0.10 s | Mitral open, aortic shut | LA 6 → 12 (a wave); LV rises to 10 | 108 → 120 (EDV) | After the P wave | S4 if present with reduced ventricular compliance |
| Isovolumetric contraction | 0.05 s | All four shut | LV 8 → 80 | 120 (no change) | During the QRS | S1 at mitral closure |
| Rapid ejection | 0.12 s | Aortic open, mitral shut | LV to peak 122; aorta follows to 120 | 120 → 65 | ST segment | — |
| Reduced ejection | 0.13 s | Aortic open, mitral shut | LV and aortic pressures fall as ejection slows | 65 → 50 (ESV) | T wave | — |
| Isovolumetric relaxation | 0.06 s | All four shut | LV 100 → 10 | 50 (no change) | End of the T wave | S2 at aortic closure; incisura on the aortic trace |
| Rapid filling | 0.14 s | Mitral open, aortic shut | LA > LV; diastolic suction assists | 50 → 96 | — | S3 may occur during rapid filling; physiological in children and young adults |
| Diastasis | 0.20 s | Mitral open, aortic shut | LA ≈ LV; slow filling | 96 → 108 | — | The phase that tachycardia abolishes first |
Two consequences of the timings in the table are worth carrying forward. Diastole shortens far more than systole when the heart rate rises: at 60 min⁻¹ diastole is about two-thirds of a 1.0 s cycle, while at 150 min⁻¹ it is closer to a third of a 0.4 s cycle. Since the left ventricle is perfused in diastole and filled in diastole, tachycardia attacks both supply and filling at once. And diastasis is the first phase to disappear, which is why moderate tachycardia is tolerated and severe tachycardia is not.
The heart sounds
| Sound | Cause | Timing | Significance |
|---|---|---|---|
| S1 | Mitral then tricuspid closure | Start of isovolumetric contraction | Loud in mitral stenosis and in tachycardia; soft in a long PR interval or poor contractility |
| S2 | Aortic then pulmonary closure | Start of isovolumetric relaxation | Splits physiologically on inspiration as increased right ventricular filling delays pulmonary closure; fixed splitting in atrial septal defect; reversed in left bundle branch block and severe aortic stenosis |
| S3 | Rapid ventricular filling | Early diastole | Normal under 40 and in pregnancy; otherwise suggests a dilated ventricle with a high filling pressure |
| S4 | Atrial contraction against a stiff ventricle | Late diastole | Always pathological; requires sinus rhythm, so absent in atrial fibrillation |
The venous pressure waveform
| Component | Mechanism | Timing against the ECG | Abnormality |
|---|---|---|---|
| a wave | Atrial contraction | After the P wave | Absent in atrial fibrillation; cannon waves in complete heart block or junctional rhythm; large in tricuspid stenosis and pulmonary hypertension |
| c wave | The closed tricuspid valve bulging into the atrium | After the QRS | Rarely visible clinically |
| x descent | Atrial relaxation and descent of the atrioventricular ring | During ejection | Lost in tricuspid regurgitation; prominent in tamponade |
| v wave | Atrial filling against a shut tricuspid valve | Near the end of the T wave | Large and fused with c in tricuspid regurgitation |
| y descent | Tricuspid valve opens and the atrium empties | Early diastole | Steep and deep in constriction; blunted or absent in tamponade |
One figure, four determinants
The pressure–volume loop
The loop plots left ventricular pressure against left ventricular volume over one cardiac cycle, and it is traced anticlockwise. Its four sides are the four phases: filling, isovolumetric contraction, ejection, isovolumetric relaxation. Its two bounding relations are what convert it from a shape into a model of the ventricle.
What can be read off the loop
| Feature | What it gives | Note |
|---|---|---|
| Width of the loop | Stroke volume | EDV − ESV |
| Right lower corner | End-diastolic volume and pressure | Mitral valve closure |
| Left upper corner | End-systolic volume and pressure | Aortic valve closure; lies on the ESPVR |
| Enclosed area | External stroke work | About 1 J per beat at rest |
| Slope of the ESPVR | Contractility (end-systolic elastance) | Load-independent |
| Position of the EDPVR | Ventricular compliance | Steeper means stiffer |
| Slope from EDV to the end-systolic point | Effective arterial elastance, Ea | A measure of afterload on the same axes |
| Width ÷ EDV | Ejection fraction | Load-dependent — not an index of contractility |
A worked calculation
An echocardiogram gives a left ventricular end-diastolic volume of 120 mL and an end-systolic volume of 40 mL. Show the calculations for stroke volume and ejection fraction. Marks require the formula, the working and the units.
If the heart rate is 70 min⁻¹, cardiac output is 80 mL × 70 = 5600 mL min⁻¹, that is 5.6 L min⁻¹. For a body surface area of 1.8 m², the cardiac index is 3.1 L min⁻¹ m⁻².
The figure below solves the loop live from the ESPVR, the EDPVR and arterial elastance for whichever heart state you pick, so the numbers under it are the geometry above it. Start on Normal and move the sliders — preload, afterload, contractility, heart rate — one at a time, which is the discipline the question rewards. Then step through the valve lesions, where the diagnosis is often in which phase is missing, and the myocardial disease states, and try the same sliders on top of each: loading conditions and the underlying lesion interact, and the figure will show you how.
One thing to expect, because it differs from most printed loops: the filling limb from mitral opening to mitral closing looks almost flat here. That is a scale effect, not a drawing error. Filling pressure runs from about 3 mmHg at the early-diastolic nadir to a left ventricular end-diastolic pressure near 10 mmHg, and a 7 mmHg rise is small on a pressure axis that has to reach 240 mmHg to contain the aortic stenosis loop on the same axes. Textbook loops are usually drawn to about 150 mmHg and exaggerate the diastolic limb for clarity. Note too that pressure falls before it rises: the ventricle is still relaxing as it fills, so the limb dips to its nadir and then climbs the passive curve.
Interactive figure -- simulation-backed
The pressure-volume loop
Pick a condition. Each loop is the converged trajectory of a time-varying-elastance ventricle driving a Windkessel arterial load -- the same solver run produced every number below the graph.
The normal loop
- This is the solver's own converged trajectory: a time-varying elastance ventricle ejecting into a three-element Windkessel, run to a limit cycle.
- Four valve events, one smooth ejection peak, and a stroke work all fall out of the physics rather than being drawn.